Skin color is primarily determined by the amount of the pigment melanin present in melanocytes, cells that are present in the epidermal basal layer of the skin. Melanin production takes place in unique organelles within the melanocytes, known as melanosomes, and protects the skin from the harmful effects of UV light. Darker skin tone of certain societies results from a naturally increased production of melanin, and high production in response to the stimulus of UV light leads to the well-known tanning effect of the skin. Aging, exposure to sun, hormonal abnormalities and various skin disorders increase the deposition of melanin pigment in skin, resulting in dark spots and freckles. Such dark spots are not only considered to be unattractive in many societies, they are also known to be unhealthy and therefore undesired.
For those who are interested in eliminating the presence of dark spots on the skin or a lighter skin tone, whitening or bleaching compositions are useful. Many modern skin-bleaching compositions either destroy melanin (typically by destroying or disrupting melanin granules), inhibit its formation (often by inhibiting tyrosinase, a melanin biosynthetic enzyme, or by inhibiting melanocyte activity and proliferation), or both. Many of these bleaching compositions contain harsh chemicals such as peroxides, acids or formaldehyde, or thiolated materials such as glutathione, cysteine, mercaptosuccinic acid, mercaptodextran, and mercaptoethanol. These chemicals, in addition to having stringent effects on skin, have an objectionable odor that makes products containing them undesirable to a consumer.
Less stringent therapies have other disadvantages. For example, hydroquinone is used as a whitening agent as it acts by suppressing melanocyte activity. However, hydroquinone is oxidized by air, light, and tyrosinase itself. The oxidized products of hydroquinone have been implicated in skin irritation and inflammation (and perhaps cytotoxicity) and in pigmentation rebound (i.e. initial lightening followed by darkening). In addition, due to these oxidation processes, the shelf life of preparations containing hydroquinone and its bioavailability upon application are relatively short.
Typical whitening agents in cosmetic formulations are kojic acid, arbutin, licorice extract and vitamin C. These are effective tyrosinase inhibitors and anti oxidants, but are usually not stable as they are easily oxidized and degraded.
European Patent No. EP0467795 discloses the use of paucilamellar liposomal carriers for transporting active molecules across the cell membrane, including molecules which induce reduction of melanosome formation by diversion of the enzymatic activity, resulting in hyperactivation of the melanin-degrading enzymes. That patent also discloses dermatological or cosmetic compositions based on these carriers and to their uses in the elimination or attenuation of dyschromia as well as in the treatment of melanoma caused by exposure to sunlight.
Recently, it has been suggested to use naturally derived materials, which are more pleasant to use, some of which have been known in ancient therapies to have whitening effects. These include the use of lemon, orange, cucumber, ginko, carob, rose fruit, geranium herb, cinnamon, sweet marjoram, rosemary, clove, mulberry, licorice, bearberry, and acerola cherry extracts, alone or in combination with other whitening agents (for example, see U.S. Pat. Nos. 5,747,006; 5,980,904; 6,994,874; and 7,029,709 among others). The variability of active ingredients in these natural products sometimes limits their usefulness, particularly as skin type, color, age, and condition vary greatly in different subjects, and make suggested dosages and regimens difficult to fashion.
Cosmetic compositions containing carotenoids having a whitening effect have been also disclosed. Japanese Patent No. JP2004300117 discloses a cosmetic composition containing carotenoids and an extract of a plant of the genus Malus, preferably the extract of the fruit or fruit juice, wherein the extract preferably contains polyphenols and the carotenoids preferably contain lycopene.
Japanese Patent No. 6279257 discloses a carotenoid or a chloroform extract of Jatropha podagrica, belonging to the family Euphorbiaceae, having an inhibitory activity on melanin biosynthesis and cosmetic compositions comprising same for beautifying and whitening skin.
However, carotenoid containing compositions are typically highly colored due to the orange-red color of beta-carotene and lycopene. Beta-carotene and lycopene are sensitive to light and oxidation, a property which considerably limits their use and shortens shelf-life of products containing them (in: Carotenoids, Chemistry and Biology, Krinski, N. I., Matthews-Roth, M. M., Taylor, R. F., eds., Plenum Press, New York, London, 1989). In addition, beta-carotene and lycopene have a distinctive orange color and this color has a serious limitation for use in effective concentrations in a variety of cosmetic or nutraceutical applications. Moreover, composition comprising colored carotenoid like lycopene, beta-carotene, cantaxanthin and the like are known to color the skin when applied topically and moreover, when taken orally, as disclosed, for example, in U.S. Pat. No. 6,110,478. Such compositions are used to achieve skin tanning effects, and commercial products for this purpose are available in the market.
Thus, there is a recognized need for, and it would be highly beneficial to have alternative, effective carotenoid preparations having minimal adverse side effects, which are effective for whitening skin and which are suitable for the cosmetic industry in topical as well as in oral forms.